National survey of pharmacists, intern pharmacists and pharmacy students in Australia: the nature and extent of stress and well-being.

OBJECTIVES: A national survey of the Australian pharmacy workforce was conducted to determine the extent to stress experienced, the extent to which it is work-related, how stress is managed, the barriers to getting help and how well prepared the workforce is for stressful situations. There were three objectives: provision of guidance on possible interventions; provision of a baseline for further studies; and provision of information to the Australian Health Practitioner Regulation Authority (AHPRA). METHODS: An online survey incorporating the 10-item Perceived Stress Scale was developed, piloted and launched in October 2016. Pharmacy-related organisations alerted their members to the voluntary survey. Popular pharmacy social media was used. Responses were analysed using SPSS and Excel. The a priori for significance was P < 0.05. KEY FINDINGS: In relation to the nature and extent of stress in the workforce and work-life balance, information provided by 1246 respondents out of a workforce of 29 819 revealed high levels of stress (PSS-10 score 20.1 ± 7.3), with those under 30 years of age and/or with 10 years or less in the pharmacy workforce reporting the highest levels. Just under half the respondents reported dissatisfaction with their work-life balances. CONCLUSIONS: Workplace stress is high, particularly among younger members of the workforce. Professional pharmacy associations, schools of pharmacy at Australian universities and AHPRA have been alerted to this issue. The survey should be repeated reasonably soon to determine if any of the key characteristics have changed, particularly if interventions are made to reduce the occurrence of workplace-related stress.

Does idiopathic congenital talipes equinovarus have an impact on attainment of developmental milestones? A multicentre international study.

PURPOSE: The Ponseti method is a well-established approach to treating clubfoot. Potentially, both the underlying pathology and adherence to post-correction bracing can affect lower limb function and age of independent standing and walking. This cohort study investigates the age at which infants with idiopathic clubfoot treated using the Ponseti method achieved three selected developmental milestones and whether or not this correlated with treatment compliance. METHODS: A prospectively collected database from four centres was visited. Inclusion criteria were patients with idiopathic clubfoot with no comorbidities or prior treatment. Age at attainment of independent standing, walking, nocturnal continence was compared across three groups: I) congenital talipes equinovarus (CTEV) children compliant with treatment; II) CTEV children non-compliant with treatment; and III) typically-developed siblings. Minimum follow-up was five years. RESULTS: In all, 130 patients (198 feet) fitted the inclusion criteria: 43:87 (F:M). Standing was achieved by a mean 12.0 months in group I (sd 2.50); 12.0 months (sd 2.0) in II and ten months (sd 3.0) in III. Walking was achieved by a mean 15 months (sd 4.0) in group I, 14 months (sd 1.75) in II and 12 months (sd 3) in III, respectively. Both the compliant and non-compliant CTEV children were significantly slower at achieving standing and walking compared to sibling controls (p < 0.0001). There was no significant difference between age of nocturnal continence between the three groups. CONCLUSION: Infants with idiopathic clubfoot treated according to the Ponseti method achieve independent standing and walking approximately two months later than their typically-developed siblings. The delay is not related to the use of the foot abduction brace. LEVEL OF EVIDENCE: III.

Multi-site placebo-controlled randomised clinical trial to assess protection following oral immunisation with inactivated non-typeable Haemophilus influenzae in chronic obstructive pulmonary disease.

BACKGROUND: Previous studies identified factors that modify response to an oral non-typeable Haemophilus influenzae (NTHi) vaccine in chronic obstructive pulmonary disease (COPD): severe COPD, moderate-severe exacerbations as end-point and a threshold prevalence of NTHi in the study population. More data are needed to confirm parameters that influence clinical outcomes. AIMS: The primary aim was to determine the efficacy of an oral NTHi vaccine (HI-164OV) in reducing the rate of exacerbations requiring systemic corticosteroids or hospitalisation in COPD. Secondary aims included effect on the proportion of patients experiencing such exacerbations, severity of infections and quality of life (St George Respiratory Questionnaire for COPD patients (SGRQ-C)). METHODS: This multi-centre, double-blind, placebo-controlled study was conducted at 21 Australian sites for 9 months in 2011. RESULTS: Three-hundred and twenty subjects with COPD, FEV1 <60% predicted and ≥1 moderate-severe exacerbations in the previous 12 months were recruited. The primary and secondary end-points for the intention-to-treat population aged 40-88 years were not achieved, and only 5% of subjects had an H. influenzae-positive sputum sample. Subsequent exploratory analysis of patients <65 years (91 subjects) indicated protection with respect to the primary and most of the secondary end-points, with SGRQ-C symptom scores lower at 3 and 6 months. CONCLUSION: Patients aged 40-88 years with moderate to severe COPD and low rates of H. influenzae-positive sputum were not protected against exacerbations by HI-1640V. Further studies are needed to confirm protection in subjects aged <65 years. Older age and low colonisation rates appear to affect adversely response to this vaccine.

Evertor muscle activity as a predictor of the mid-term outcome following treatment of the idiopathic and non-idiopathic clubfoot.

Previous studies have identified clinical and demographic risk factors for recurrence in the treatment of idiopathic clubfoot (congenital talipes equinovarus). Evertor muscle activity is not usually considered amongst them. This study aimed to evaluate whether recurrence could be predicted by demographic, clinical and gait parameters. From a series of 103 children with clubfeet, 67 had completed a follow-up of two years: 41 male and 26 female, 38 with idiopathic and 29 with non-idiopathic deformities. The mean age was 3.2 years (2.1 to 6.3). Primary correction was obtained in all 38 children (100%) with an idiopathic deformity, and in 26 of 29 patients (90%) with a non-idiopathic deformity. Overall, 60 children (90%) complied with the abduction brace regime. At a mean follow-up of 31.4 months (24 to 62), recurrence was noted in six children (15.8%) in the idiopathic and 14 children (48.3%) in the non-idiopathic group. Significant correlation was found between poor evertor activity and recurrence in both groups. No statistically significant relationship was found between the rate of recurrence and the severity of the initial deformity, the age at the time of treatment, the number of casts required or the compliance with the brace. After correction of idiopathic and non-idiopathic clubfoot using the Ponseti method, only poor evertor muscle activity was statistically associated with recurrence. The identification of risk factors for recurrent deformity allows clinicians to anticipate problems and advocate early additional treatment to improve muscle balance around the ankle.

Oral non-typable Haemophilus influenzae enhances physiological mechanism of airways protection.

Oral immunotherapy with inactivated non-typeable Haemophilus influenzae (NTHi) prevents exacerbations of chronic obstructive pulmonary disease, but the mechanism is unclear. The aim of this study was to determine the mechanism of protection. This was a placebo versus active prospective study over 3 months in 64 smokers. The active treatment was three courses of oral NTHi given at monthly intervals, followed by measurement of bacteriological and immunological parameters. The results can be summarized: (i) NTHi-specific T cells increased in the placebo treatment group over time (P<0.05); (ii) the T cell response in the oral NTHi group started earlier than that in the placebo group (P<0.05); and (iii) serum NTHi-specific immunoglobulin (Ig)G had significantly greater variation in the placebo group (P<0.0001). The increase in antibody in placebos over time correlated with exposure to live H. influenzae (P<0.05) determined from culture of gargles; (iv) reduction in saliva lysozyme over time (P<0.05) was detected only in the oral NTHi treatment group. These data are consistent with T cell priming of gut lymphoid tissue by aspiration of bronchus content into the gut, with oral immunotherapy augmenting this process leading to enhanced bronchus protection. The evidence for protection was a stable IgG antibody level through the study in the oral NTHi treatment group, contrasting with an increase in antibody correlating with exposure of the airways to H. influenzae in the placebo group. Saliva lysozyme was a useful biomarker of mucosal inflammation, falling after oral NTHi consistent with a reduction in the level of intralumenal inflammation.

Evaluation of anti-Helicobacter pylori IgG2 antibody for the diagnosis of Helicobacter pylori infection in western and Chinese populations.

BACKGROUND: The performance of commercial Helicobacter pylori diagnostic kits developed for particular geographic regions has often been found to be of poor diagnostic value when applied to other regions, possibly because of infections being caused by different H. pylori strains in different regions. AIM: To evaluate the performance of an IgG2 anti-H. pylori enzyme-linked immunoassay test (Helirad Alert) for detection of H. pylori infection in both Australian and Hong Kong (Chinese) subjects. METHODS: Serum samples were tested for H. pylori specific IgG2 and IgG antibodies by enzyme-linked immunoassay kits using identical antigen preparation in 168 Australian and 160 Hong Kong (Chinese) subjects diagnosed with dyspepsia. RESULTS: Using a cut-off value determined by analysis of H. pylori-negative Australian samples, the sensitivity, specificity and accuracy of the IgG2 assay were 77.8, 97.4 and 91.1%, respectively, for the Australian samples and 96.3, 83.8 and 90% for Hong Kong samples. For the IgG assay, sensitivity, specificity and accuracy were 87.0, 99.1 and 95.2% for Australian samples and 97.5, 75 and 86.3% for Hong Kong samples respectively. Receiver-operating characteristic analysis showed better discrimination of H. pylori status when the IgG2 assay was applied to Hong Kong samples, while the IgG assay was better in the Australian samples. CONCLUSION: These data demonstrate that the Helirad Alert enzyme-linked immunoassay could provide a reliable method for screening H. pylori infection in both western and Chinese populations.

Shift of the gastric T-cell response in gastric carcinoma.

BACKGROUND AND AIMS: The etiology and pathophysiology of stomach carcinoma is complex, and the mechanism whereby H. pylori directly or indirectly induces carcinoma remains unclear. In this study, interleukin (IL)-8, IL-4 and interferon (IFN)-gamma were measured in the tissue culture supernatant of gastric organ cultures from subjects with chronic gastritis with or without H. pylori infection, and with or without gastric cancer and gastric dysplasia. RESULTS: Interleukin-8 levels were higher in cancer- and H. pylori-infected gastritis subjects than in H. pylori-negative subjects (12.95 +/- 3.16, 10.48 +/- 1.55 and 4.49 +/- 1.28 ng/mL, respectively). Elevated levels of IFN-gamma were detected in both H. pylori-infected and non-infected subjects with uncomplicated gastritis (72.23 +/- 19.0 and 34.61 +/- 5.30 pg/mL) and in non-infected dysplasia subjects (88 +/- 20.5 pg/mL). Background levels of IL-4 (< or = 9.4 pg/mL) in uncomplicated gastritis subjects and relatively high levels of IL-4 in dysplasia subjects (25.8 +/- 7.3 pg/mL) were detected. In contrast, trace amounts of IFN-gamma (16.01 +/- 0.35 pg/mL) and high levels of IL-4 (42.81 +/- 8.49 pg/mL) in gastric biopsy culture supernatants were found in cancer subjects. Mucosal IL-4 levels (but not IL-8 levels) correlated with infection and mucosal anti-H. pylori immunoglobulin G antibody. CONCLUSIONS: The significant differences between gastritis with and without cancer and dysplasia indicated a shift from a Th1 to a Th2 helper cell pattern of cytokine secretion. This study has identified a local mucosal defect in gastric cancer. The near absence of IFN-gamma production from the mucosa at the margins of the tumor may be a critical factor in promoting growth of neoplastic cells.

Non-urease producing Helicobacter pylori in chronic gastritis.

BACKGROUND: Helicobacter pylori infection is the commonest cause of gastritis. Different patterns of immune response to H. pylori infection and characteristics of bacteria are considered to contribute to clinical outcomes. AIM: To determine characteristics of the host H. pylori relationship in subjects with non-ulcer dyspepsia and a histological diagnosis of gastritis. METHODS: Thirty-five subjects with chronic gastritis undergoing endoscopy (mean age 53 years, range 24-82, 14 male and 21 female) were studied, none of whom was on nonsteroidal anti-inflammatory drugs or antibiotics. H. pylori infection was determined by rapid urease test (CLOtest), culture, antibody and RT-PCR for Ure C, Cag A and 26 kDa gene and histology. Cytokine production of mucosal IL-6 and IL-8 were measured by ELISA. RESULTS: Fifteen subjects were positive by CLOtest and/or bacterial culture. In these subjects histology showed numerous helical forms of H. pylori (Group I). Nine subjects were negative by CLOtest, bacterial culture, and mRNA for urease C fragment, but positive by PCR for the 26 kDa protein encoding gene. Histology in these subjects showed the presence of either coccoid forms (four), or scant helical forms (two), or mixed coccoid/helical forms (three) (Group II). Eleven subjects were negative by all methods of detection (Group III). IgG and IgA antibody levels in serum (p<0.05) and gastric tissue culture supernatant (p<0.001) were significantly higher in Group I than those in Group II or III. There were significant differences in the IgG serum and IgA supernatant antibody levels (p<0.01 and p<0.05) when Group II was compared to Group III. Supernatant IL-6 levels were significantly higher in Group I (p<0.01) than those from Groups II and III. IL-8 levels were higher in Group I (p<0.01) and Group II (p<0.05) when compared to Group III. CONCLUSIONS: 'H. pylori-negative' gastritis can be associated with a non-urease producing form of H. pylori, with a reduction in both local and systemic antibody levels and mucosal pro-inflammatory cytokines.

Training specialist registrars in general surgery: a qualitative study in Tayside.

BACKGROUND: Owing to decreased hours of work and duration of training, there is a need to refashion the training of surgical specialist registrars (SpRs) in the United Kingdom. This requires more guidance for trainers, but consensus regarding good trainer attributes does not exist. This study describes the training practices of Tayside general surgical trainers working with SpRs and highlights good training practice involving technical and patient management skills. METHODS: 1) Semi-structured interviews carried out with eighteen consultant trainers and twelve SpRs, 2) Action inquiry (i.e. observations and dialogue with participants) during ward, theatre, outpatient clinic and other hospital-based settings with eleven consultant and SpRs pairs. RESULTS AND CONCLUSION: Participants reflected on multiple training episodes and evaluated their impact. Relatively positive or negative impacts on their skill learning, self-esteem and relationship with the trainee or trainer were described. These are presented and discussed in terms of their implications for equipping trainers with techniques for training registrars and those factors which have hindered the adoption of successful strategies.

Circulating T-cell response to Helicobacter pylori infection in chronic gastritis.

BACKGROUND: Helicobacter pylori elicits a specific humoral and cellular immune response. There is increasing evidence that the type of T-cell response contributes to clinical outcome in H. pylori infection. MATERIALS AND METHODS: The host response to H. pylori infection in 34 subjects with chronic gastritis was examined in terms of T-cell proliferation and cytokine production in whole-blood cultures stimulated or unstimulated with H. pylori acid-glycine extract antigens (AGE). RESULTS: The proliferative response in whole-blood cultures was similar for both H. pylori-positive and -negative subjects stimulated with H. pylori AGE. While an increase in interferon-gamma (IFN-gamma) production was observed from both H. pylori-positive and -negative subjects with gastritis, significantly higher levels of IFN-gamma were detected in the former when stimulated with H. pylori AGE. In contrast, interleukin 4 (IL-4) was undetectable regardless of antigen stimulation. However, if an in situ IL-4 antibody capture assay was used, antigen-independent production of IL-4 was detected, but there was no difference between H. pylori-positive and -negative subjects with gastritis. After eradication of H. pylori, antigen-induced production of IL-4 was increased, with no decrease in the levels of secretion of IFN-gamma. IL-4 production was dependent on CD4+ T cells, as addition of anti-CD4 but not anti-CD8 mouse monoclonal antibody or matched IgG isotype to the whole-blood culture inhibited the production of IL-4. CONCLUSION: The results suggest that a shift toward a balanced Th1-Th2 response due to an increase in antigen-induced IL-4 production from CD4+ T cells follows eradication. We suggest that the downregulation of mucosal inflammation consequent on reduction in antigen levels or removal of downregulation after eradication of H. pylori contributes to this shift in cytokine balance.

Catalase immunization from Pseudomonas aeruginosa enhances bacterial clearance in the rat lung.

Pseudomonas aeruginosa is a common cause of infection in immunocompromised patients and is the major contributor to morbidity in individuals with cystic fibrosis (CF). The antibiotic resistance shown by this pathogen and morbidity in patients with chronic infection has encouraged investigations into the development of a vaccine. This study reports the purification of a 60 kDa protein, isolated from a mucoid strain of P. aeruginosa, identified by amino acid sequence analysis as the catalase protein (KatA). A rat model of acute P. aeruginosa respiratory infection was used to investigate the immunogenicity of KatA and determine the potential of mucosal immunization with KatA to protect against infection. Immunization regimens compared a single intra-Peyer's patch (IPP) immunization with an IPP primary inoculation followed by an intratracheal boost to the lungs. Mucosal immunization with KatA resulted in significant pulmonary clearance of both homologous (p<0.001) and heterologous (p<0.05) strains of P. aeruginosa. Both immunization regimens enhanced bacterial clearance, increased the rate of recruitment of phagocytes to the bronchoalveoli and induced KatA-specific antibody. However, the regimen that included a boost induced a more effective immune response that also resulted in better clearance of P. aeruginosa from the lungs. Mucosal immunization induced KatA- specific antibodies in the serum and the bronchoalveolar lavage, and KatA-specific lymphocyte proliferation in vitro in cells isolated from the mesenteric lymph nodes of immunized rats. The data presented suggests that KatA has the potential to afford a protective immune response against pulmonary infection by P. aeruginosa

Patch incorporation in diaphragmatic hernia.

BACKGROUND/PURPOSE: Biomaterial insertion often is required for closure of congenital diaphragmatic hernia (CDH). The optimal biomaterial remains uncertain. This study was designed to compare a commonly used patch (polytetrafluoroethylene) with a recently available fabric, fluorinated polyester. The aim of this study was to determine the clinical performance, histological tissue-polymer interaction, bacterial adhesion, and shrinkage rates of biomaterial inserted endoscopically into a CDH lamb model. METHODS: Polytetrafluoro-ethylene (PTFE) and fluorinated polyester (FP) were randomised for laparoscopic patch insertion into 12 lambs. All lambs (age <4 weeks) underwent 3-port laparoscopy, surgical creation of diaphragmatic hernia, and sutured patch placement. Two PTFE and 2 FP lambs were killed at 1-, 3-, and 6-month intervals postoperatively. Postmortem examination histopathology, electron microscopy, and specific bacterial broth immersion (Escherichia coil, Staphylococcus aurens, and epidermidis) were performed. RESULTS: All 12 lambs completed the study with intact patches that were fully peritonised. One abdominal adhesion was noted in a FP lamb at 6 months. FP was comparatively easier to insert, manipulate, and suture endoscopically. Histopathology findings showed that PTFE patches created a strong peripheral foreign body reaction with dystrophic calcification, whereas FP was well incorporated with intrapatch fibroblastic activity and neovascularsation. No significant difference in resistance to bacterial adhesion of relevant organisms was noted between the materials. Graft shrinkage for FP was 7% in one direction only, evident by 3 months. CONCLUSIONS: Fluorinated polyester has advantages in this laparoscopic lamb model. It shows rapid and sustained incorporation with intrapatch neovascularisation when compared with polytetrafluoro-ethylene's significant foreign body reaction. It was preferred for its endoscopic handling and suturing properties. The laparoscopic techniques used may contribute to the general lack of adhesions, and insufficient data are available to comment on the comparative effect of the materials on adhesion formation. No difference was demonstrated in resistance to bacterial adherence in the harvested materials.

A randomised control trial of surgical task performance in rigid bronchoscopy: foreign body extraction with optical versus non-optical forceps.

There are currently two types of forceps used for foreign body removal at rigid bronchoscopy, these can be classified as standard bronchoscopy forceps and optically guided grasping forceps. In order to evaluate them in the removal of foreign bodies from the tracheo-bronchial tree a randomised subject controlled trial was conducted. All 80 bronchoscopies were recorded and analysed by a single observer according to predetermined criteria for surgical error. The data was analysed using a t-test for paired groups. The results showed no significant differences between the two groups. We conclude that no clear advantages were found comparing the optically guided forceps with the standard bronchoscopy forceps and that further clinical evaluation will be difficult to initiate.

Coccoid forms of Helicobacter pylori can be viable.

Controversy exists as to whether the coccoid form of Helicobacter pylori can exist in a viable form. Conversion of helical to coccoid morphology occurs in culture over several days. In this study, the morphology was correlated with parameters of genetic integrity in the reference NCTC 11637 strain over 21 days of culture. The capacity to regrow colonies of helical form was demonstrated from a culture where the coccoid form constituted up to 95% and negligible urease activity could be detected. Urease enzyme activity and its mRNA decreased between day 0 and 10 while 26 kD mRNA and 16S rRNA were expressed unchanged for up to 14 and 21 days of culture, respectively. Expression of mRNA for the Cag A gene behaved in a similar fashion to that of urease. No evidence of DNA fragmentation was detected. These data suggest that a viable form of non-urease producing H. pylori exists after short to intermediate culture and that some if not all of these viable bacteria have coccoid morphology.

Protection against Helicobacter pylori infection by intestinal immunisation with a 50/52-kDa subunit protein.

A mouse model of Helicobacter pylori infection was used to evaluate the vaccine antigen potential of the citrate synthase homologue protein purified from the H. pylori NCTC 11637 strain. Mice were immunised with the protein by intra-Peyer's patch immunisation. This route gives maximal intestinal immunisation and was used to screen oral vaccine candidate antigens without the added complication of simultaneously testing oral delivery systems. Two weeks post-immunisation mice were infected with Sydney strain H. pylori and 4 weeks after infection the mice were killed and the level of H. pylori infection in the stomach determined. Pre-immunisation with the 50/52-kDa protein led to a 84-91% reduction in H. pylori infection compared to unimmunised controls.

Increased severity of Candida vaginitis in BALB/c nu/nu mice versus the parent strain is not abrogated by adoptive transfer of T cell enriched lymphocytes.

The role of the host immune system in combating candidal infections in the vagina is poorly understood. A murine model of Candida vaginitis was used to elucidate the role of T cells in a candidal infection. Athymic BALB/c nu/nu mice or normal BALB/c mice were induced into estrus and then infected with 1 x 10(6) Candida albicans intravaginally. The infection was monitored over 1 week. Samples from blood, small intestine, tongue, kidney, spleen, liver, uterus and vagina were tested for recoverable C. albicans. Histology of the vagina was assessed for both inflammation and extent of infection. Results indicated that the BALB/c nu/nu mice had similar levels of vaginal yeast load to the normal BALB/c mice. In 25-30% of nude mice Candida was also recovered from extra vaginal sites (kidney, liver, small intestine), however, extra vaginal dissemination was not observed in any normal BALB/c animals. Histologically, both the nu/nu and control BALB/c had similar levels of vaginal inflammation; however, the nu/nu mice had more florid fungal growth in the vaginal epithelium. Adoptive transfer of either immune or non-immune BALB/c T cells into nude mice had no affect on either infection or vaginal inflammation. Immunohistochemical staining of vaginal tissues from normal BALB/c mice or nude mice adoptively transferred with either immune or non-immune T cells with anti-CD3 monoclonal antibody revealed no significant difference between groups in the numbers of CD3+ vaginal T cells. However, in mice receiving either immune or non-immune T cells no yeast was recovered from any tissues except the vagina. These data show that T cells have a limited role in protecting the vagina from C. albicans infection.

Cellular immunity in recurrent vulvovaginal candidiasis.

Impaired T cell function has been reported to predispose women to recurrent vulvovaginal candidiasis, but conflicting results have been noted in the literature. Most clinical episodes occur in the late luteal phase, suggesting hormonal influence on host resistance. The present study assesses the cellular immune responses of 28 women with recurrent vaginal candidiasis (patients) and 25 control women (controls), noting results in relation to whether the women were in the follicular or luteal phase of the menstrual cycle at the time of sampling. Candida-stimulated peripheral blood lymphocyte proliferation was significantly reduced in patients compared with controls. Interferon-gamma (IFN-gamma) production in response to both Candida and purified protein derivative (PPD) stimulation was significantly lower in patients compared with controls. Skin test responses were comparable in both groups. A significant reduction in Candida-stimulated IFN-gamma production was seen in patients but not controls in the follicular phase compared with those in the luteal phase. There was also a trend towards lower proliferation in response to Candida in patients but not controls in the follicular phase compared with patients in the luteal phase. These results suggest that there is a partial T cell dysregulation in recurrent vaginal candidiasis which may be exacerbated by the hormonal balance present during the follicular phase, correlating with the risk of clinical infection.

Acute neutropenia decreases inflammation associated with murine vaginal candidiasis but has no effect on the course of infection.

We have used a mouse model of vaginal candidiasis to determine the effect of neutrophil depletion on (a) the clearance of Candida albicans and (b) the degree of inflammation associated with infection. No differences in recoverable yeast number or rate of clearance were observed between normal and neutrophil-depleted mice; however, vaginal inflammation was significantly decreased in neutrophil-depleted animals.